Diptheria toxin-interleukin 3 fusion protein therapy of patients with elderly or relapsed/refractory acute myeloid leukemia (AML)
Bibliographic record
Abstract
6569 Background: To target myleoid leukemic stem cells in relapsed/refractory patients, we produced a recombinant protein composed of the catalytic and translocation domains of diphtheria toxin (DT388) fused to human interleukin 3 (IL3). DT388IL3 binds to IL3 receptors on leukemic progenitors; the toxin is internalized and enzymatically inactivates protein synthesis leading to programmed cell death. We prepared a clinical batch of DT388IL3 and obtained FDA approval for a phase I study. Patients and Methods: Relapsed/refractory or elderly (≥70 years) AML patients with normal organ function and low anti-DT antibody titers were consented and given 15 minute infusions of DT388IL3 on a M-W-F for two weeks schedule. Premedication was hydrocortisone, acetaminophen, and diphenhydramine. Inter-patient dose escalation was done. Five patients at 4 ug/kg, 6 patients at 5.32 ug/kg, and 2 patients at 7.07 ug/kg received all 6 planned doses. Results: Eighteen patients have been treated as of 1/06. Median age was 58 years (25–81). There were 9 males and 9 females. One patient had de novo AML; 7 patients were in second relapse; 6 patients were in third relapse and 4 patients had refractory AML. One patient each received an autologous stem cell transplant (SCT), and an allogeneic SCT. Cytogenetics were unfavorable in 3, intermediate in 10 and not done in 5 patients. One patient each had MDS-related AML and treatment-related AML. Drug-related side effects were mild and transient including grade 3 fever, grade 2 hypotension, chills and hypoalbuminemia. Responses seen to date have been transient including a reduction in bone marrow blast index (% cellularity × fraction blasts) of pretreatment 40%, 70%, 36% and 40% converting to 8%, 4%, 4% and 4% on day 15. Conclusions: The preliminary data suggests mild toxicity with biological activity. Dose escalation is planned as per protocol. No significant financial relationships to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".